Each year in the United States, there is significant loss of vision as a result of uveitis of unknown etiology. There is evidence to indicate that autoimmunity may play a role in some of these uveitides. Investigation into such an immunologic etiology has necessitated the development of animal models, such as footpad presentation of retinal or uveal autoantigens in adjuvant to produce an experimental autoimmune uveitis (EAU). In both clinical and experimental studies evaluation of the immune response has relied heavily on systemic measurements of immune responsiveness. There is limited experimental evidence to indicate that such measurements of cells or antibodies recovered from extraocular tissues are reflective of those portions of the immune response that are operative in the eye during uveitis. The work of this laboratory is currently directed toward defining the relationship of the systemic and ocular immune responses in uveitis, specifically in EAU. The specific aims of this proposal are: 1) to continue characterization of various components of the systemic and local (ocular) immune response during the development of EAU induced by both high and low doses of S antigen, since these doses produce different clinicopathologic forms of EAU. These experiments will specifically focus on the initial stages of EAU with attention to a) anti-S reactivity in aqueous, vitreous and serum as measured by ELISA, b) immunoglobulin deposits on the retina as demonstrated by immunofluorescence and characterized by adoptive transfer, and c) histochemical and immunohistochemical identification of cell populations infiltrating different portions of the eye. 2) to characterize the systemic and local immune responses of EAU induced by uveal homogenate (U antigen) and of EAU induced by retinal sediment (P antigen). These models have been identified but not fully characterized. Since the uveitis produced in these models is posterior, a comparison with the S antigen model should provide an understanding of the relationship of anterior and posterior uveitis. These models are also important since not all human autoimmune responses to ocular antigens need be to S antigen. 3) to continue the studies on subcellular localization of anti-S, anti-U, and anti-P reactivity on normal retina, as an extension of our light microscopic immunofluorescent localization studies of these sera.